Pteridine reductase

Function

Pteridine reductase (PTR) catalyzes the reduction of 5,6,7,8-tetrahydrobiopterin (THBP) to biopterin. PTR is part of pterin and folate metabolism^[1]. NADP is the hydrogen acceptor in this reduction.

Relevance

PTR is essential for growth of trypanosomatid protozoans like Leishmania parasites, thus PTR inhibitors like methotrexate (MTX) or triaminoquinazoline (TAQ) are tested as potential drugs^[2].

Structural highlights

^[3]. Water molecules are shown as red spheres.

Structure of pteridine reductase complex with NADPH, tetrahydrobiopterin, ethanediol and ethylene glycol (PDB entry 2bfp)

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3D structures of pteridine reductase3D structures of pteridine reductase

Updated on 03-October-2023

ReferencesReferences

↑ Bransteitter R, Pham P, Scharff MD, Goodman MF. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4102-7. Epub 2003 Mar 21. PMID:12651944 doi:http://dx.doi.org/10.1073/pnas.0730835100
↑ Cavazzuti A, Paglietti G, Hunter WN, Gamarro F, Piras S, Loriga M, Allecca S, Corona P, McLuskey K, Tulloch L, Gibellini F, Ferrari S, Costi MP. Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1448-53. Epub 2008 Feb 1. PMID:18245389
↑ Schuttelkopf AW, Hardy LW, Beverley SM, Hunter WN. Structures of Leishmania major pteridine reductase complexes reveal the active site features important for ligand binding and to guide inhibitor design. J Mol Biol. 2005 Sep 9;352(1):105-16. PMID:16055151 doi:http://dx.doi.org/10.1016/j.jmb.2005.06.076

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Bransteitter R, Pham P, Scharff MD, Goodman MF. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4102-7. Epub 2003 Mar 21. PMID:12651944 doi:http://dx.doi.org/10.1073/pnas.0730835100

[2] Cavazzuti A, Paglietti G, Hunter WN, Gamarro F, Piras S, Loriga M, Allecca S, Corona P, McLuskey K, Tulloch L, Gibellini F, Ferrari S, Costi MP. Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1448-53. Epub 2008 Feb 1. PMID:18245389

[3] Schuttelkopf AW, Hardy LW, Beverley SM, Hunter WN. Structures of Leishmania major pteridine reductase complexes reveal the active site features important for ligand binding and to guide inhibitor design. J Mol Biol. 2005 Sep 9;352(1):105-16. PMID:16055151 doi:http://dx.doi.org/10.1016/j.jmb.2005.06.076

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